Creatine Technical Document Feb Creatine. Technical Document

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1 Creatine Technical Document Developed by INDI/SNIG for the Irish Sports Council 2014

2 Creatine Databases Pubmed and Google Scholar were searched for human studies published in peer-reviewed journals from Search terms: Creatine, Creatine Monohydrate, Athletes, Sport, Exercise. The reference list from the creatine articles retrieved was searched for any additional papers that were relevant to the development of this document and the history of creatine in sport. Inclusion Criteria Human studies published in English Healthy subjects Original investigations assessing the use of creatine and exercise Incorporated the use of an indistinguishable placebo Sufficient statistical power Reviews Exclusion Criteria Combined supplement studies Qualitative studies assessing supplement use in both the general and athletic population Animal/in vitro studies 8 studies and 1 review satisfied the inclusion criteria with findings outlined in table 1. (For studies published see table 2) Introduction Creatine is a compound derived from amino acids, produced endogenously by the liver and to a lesser extent by the kidneys and pancreas (Burke et al. 2003; Cooper et al. 2012). Creatine is synthesised from three amino acids, arginine, glycine and methionine that are predominantly located in skeletal muscle (SM) tissue (Bemben and Lamont 2005). Following hepatic production, creatine is transported via the circulatory system to target tissues/organs including the brain and SM. SM is the storage site for approximately 95% of creatine and here, uptake is primarily facilitated by sodium-chloride-dependent Creat1 transporter proteins that enable creatine accumulation within SM (Persky et al. 2003; Schoch et al. ). However it is important to recognise that SM creatine stores have a finite capacity owing to the intrinsic

3 downregulation of Creat1 transporters, resulting in excretion of excess creatine via urine. Approximately 60% of creatine exists in its phosphorylated form, phosphocreatine (PCr). There are many proposed mechanisms of action by which creatine supplementation may promote maximal performance. These have been reviewed in detail (see Persky et al or Cooper et al. 2012). Sources Creatine can be derived from consumption of a limited range of food products including red meat (350mg creatine/100g), eggs and fish (Williams, 2007). Alternatively creatine can be obtained by consuming creatine monohydrate supplements, available in powdered or liquid form. Creatine monohydrate supplementation has a long history in a wide range of sports including weightlifting, American football, soccer, handball, track sprinting, squash, track-and-field athletes and cyclists.the powdered form of creatine appears to be the most commonly used in the literature and also in the field. Creatine in liquid form has been used in research, but has failed to demonstrate ergogenic effects when compared with creatine consumed in powder form. This lack of benefit from liquid creatine supplementation is likely due to the small amount of creatine found in such products (Gill et al. 2004, Harris et al. 2004). It is also important to recognise that creatine is not stable in solution, and those products sold in liquid form are unlikely to contain any significant amount of creatine. Dosage According to the International Society for Sports Nutrition position statement (2007), the following is defined as an effective creatine supplementation protocol: Loading phase of 0.3g/kg/day creatine monohydrbufbate/day for at least 3days Followed by 3-5g/day to maintain elevated stores (Buford et al. 2007) Proposed benefits ATP/PCr activity PCr is an essential component of the ATP/PCr energy system which provides rapid oxygenindependent energy during the initial 30 seconds of maximal activity. Sports primarily utilising this system include track sprinting, weightlifting, and athletic events such as high jump and shot put (Burke et al. 2003). Skeletal muscle anabolism

4 Creatine may promote SM hypertrophy by up-regulating anabolic compounds such as insulin-like growth factor (IGF-1) (Burke et al. 2008). Creatine supplementation is associated with increased contractile protein content and SM fibre cross-sectional area, although this does not always translate into enhanced performance and has only been demonstrated when combined with carbohydrate and protein (Cribb et al. 2007). Glucose transport and glycogen depletion Glucose transporter proteins (GLUT) facilitate glucose absorption and enable the accumulation of glycogen within SM stores. Creatine supplementation has been shown to increase the number of these proteins, suggesting that creatine may hinder early-onset glycogen depletion in endurance athletes (Cooper et al. 2012). Oxidative stress/damage Recent studies in this field have yielded mixed results depending on the inflammatory marker analysed, with many showing no beneficial effect of creatine on exercise-induced oxidative stress/damage (Deminice et al. 2011; Rahimi 2011). Further studies are required in order to identify or rule out an antioxidant effect of creatine following intense exercise. Psychomotor ability Creatine may help to counter cognitive deficits following sleep deprivation, although causality is yet to be established (McMorris et al. ; Cook et al. 2011). Hydration status It is well documented that creatine consumption results in intracellular water retention, increasing bodyweight and that this process is catalysed in the presence of carbohydrate. This may be of benefit to athletes training in hot and humid environments by attenuating thermal and cardiovascular strain under these conditions (Beis et al. 2011). Concerns Contamination A recent study highlighted that in 33 commercially available creatine supplements, 50% contained contaminants including heavy metals, at levels exceeding the maximum limit recommended by the European Food Safety Authority in 2004 (Moret et al. 2011). It is therefore advisable to consult a performance nutritionist before consuming any creatine-based or creatine-containing supplement. Weight-class athletes

5 As mentioned above, creatine promotes intracellular water retention, increasing bodyweight. This should be taken into account when weight-class athletes are considering creatine supplementation. Range of movement A recent study also suggests that intracellular water retention from acute creatine supplementation may hinder athlete s upper and lower-body range of movement. The study speculates that this may be due to the water retention directly or via reduced neural outflow and increase anterior compartment pressure (Sculthorpe et al. 2010). Table 1: Recent Literature Supporting a Role of Creatine Supplementation in Performance (2009-Present) Reference Subjects Dose Sport/Exercise Protocol Performance Enhancement Summary Barros et al. 16 physically 20g/day for 7 days Wingate test Increased anaerobic power, capacity total (2012) active (dissolved in 500ml workload. Reduced fatigue index score water) Creatine supplementation may contribute to improved maximal anaerobic performance Cook et al. 10 elite male 50 or 100 mg/kg Rugby passing Reduced perception and skill performance, (2011) rugby bodyweight creatine skill test following sleep deprivation was ameliorated (1.5 hours prior to following creatine supplementation test) Creatine supplementation may benefit athletes that have had limited sleep due to travel De Oca et al. 12 male 50mg/kg bodyweight Taekwondo Creatine supplementation increased fat mass but (2013) taekwondo for 6 weeks had no effect on anaerobic power (dissolved in 500ml water) Deminice et al. 23 male 0.3g/kg bodyweight 6X35m sprint Supplementation had no effect on post-exercise (2013) soccer for 3 days (tablet with 10 homocysteine levels form) seconds rest between runs Percario et al. 9 elite male 20g/day for 5 days Bench press, Supplementation resulted in improved muscle (2012) handball followed by 5g/day Inclined Chest strength when compared to placebo and control for 27 days (dissolved Fly, Lat pull groups in1 00ml water) down, Seated Row, Shoulder press, Biceps curl, Squatting,

6 Leg Extension. Rahimi (2011) 27 resistance- 4X5g/day for 7 days 7 sets of 3 6 Supplementation reduced biomarkers of trained men repetitions of oxidative damage and improved athletic bench press, performance outcomes compared to a placebo leg press, lat group pull down, seated rows with 80 90% of 1RM Tang et al. 12 male 12g/day for 15 days 100m sprint Supplementation significantly increased (2014) athletes followed by a 5 day bodyweight and biomarkers of glycogen washout period degradation were reduced compared to baseline Zuniga et al. 22 healthy 20g/day for 7 days or Wingate test, Supplementation resulted in improved mean (2012) men a maltodextrin-based 1RM bench power (Wingate test) but had no effect on peak placebo press, 1RM leg power, strength, bench press, leg extension or extension bodyweight outcomes. Table 2: Literature Supporting a Role of Creatine Supplementation in Performance (- 2009) Reference Subjects Dose Sport/Exercise Protocol Performance Enhancement Summary Chilibeck et al. 18 rugby 0.1 g kg 1 d 1 CrM Players trained 2 x CrM supplementation during a rugby union 2007 union or placebo per day for per week for approx season is effective for increasing muscular football 8 weeks. 2 hours and played endurance, but has no effect on body one 80 min game per composition or aerobic endurance. week. Reardon et al. 13 healthy 6g of CrM or placebo 4 week endurance CrM supplementation does not effect physically 4 x per day for 7 days training program metabolic adaptations to endurance active, 9 male training. and 4 female. McMorris et al. 5 male and 5g of CrM or placebo Subjects completed CrM supplementation had a 13 male sport science students 4 times per day for 7 days tests of random movement generation, verbal and spatial recall, positive effect on mood state and tasks that place a heavy stress on the prefrontal cortex. choice reaction time, static balance and

7 mood state pre-test & after 6, 12 and 24 h of sleep deprivation, with intermittent exercise. McConnell et al 7 well trained 21g of CrM or placebo 45 min cycling at Increased muscle CrM before exercise 2005 per day for 5 days 78% VO2peak then a improved the ability to maintain energy time trial balance during intense exercise. Ostojic et al young 3 x 10g doses of CrM Soccer specific drills CrM ingestion improved soccer specific male soccer or placebo for 7 days. before and after drills in young. supplementation. Koenig et al active 25g of CrM, Repeated jump height The carbohydrate and CrM groups carbohydrate or before and after maintained repeated bouts of high-intensity placebo for 5 supplementation activity as measured by repeated static consecutive days. jumps. Herda et al healthy 5g of CrM, small dose High intensity CrM increased body mass and muscle of polyethylene anaerobic activities strength, but did not impact on peak power glycosylated creatine, such as 1RM and output, mean power output, or muscle moderate dose of Wingate assessed endurance when compared to placebo. polyethylene before and after glycosylated Creatine supplementation or a placebo for 30 days. Cramer et al healthy 10.5g of CrM or 3 days of isokinetic Peak torque increased but acceleration placebo 2 x per day for resistance training decreased from pre to post training. days 1-6 and 1 x per day for days 7-8. Wright et al physically 4 x 5g of CrM per day 6 x 10 sec maximal CrM does not produce any active or placebo for 6 days sprints of cycle thermoregulatory responses to intermittent ergometer in a hot sprint exercises in the heat. environment Silva et al female 20g of CrM or placebo 2 x 25m swimming CrM supplementation produced significant swimmers for 21 days bouts with 3 min effects on gross and propelling efficiency recovery pre and post during swimming but did not influence supplementation performance, body composition or body weight. Hoffman et al. 40 physically 6g of CrM or placebo Wingate test before Reduce fatigue rate was seen in subjects 2005 active for 6 days and after supplemented with CrM but no other

8 supplementation differences observed. Cornish et al g of CrM per kg of Repeated sprints till CrM was not effective in enhancing competitive body mass per day for exhaustion on skating performance in ice-hockey. male ice- 5 days or placebo treadmill hockey Okudan et al. 23 untrained 5g of CrM or placebo Wingate test before CrM supplementation enhanced total x daily for 6 days and after power output during the Wingate test. supplementation Cancela et al. 14 male 15g of CrM or placebo Football specific t assessed CrM supplementation had no negative 2008 footballer for 7 days, then 3g of training effects on blood and urinary clinical health CrM or placebo for 49 markers. CrM supplementation may be days. associated with increased creatine in case activity, improving efficiency of ATP resynthesis. Sale et al healthy 4 x 5g day-1 CrM for 24 hour urine t assessed Less CrM was excreted when CrM was 5 days or 20 x 1g day- collections at dat 1-2 ingested as 20x 1g doses, which suggests 1 CrM for 5 days and 3-7 post greater retention by the body and probably supplementation. the muscles. Gotshalk et al. Thirty CrM (0.3g kg BM) or 1RM resistance Short term CrM supplementation resulted 2008 year old placebo for 7 days training assessments in increased strength, power, and lower- fe + lower body and body motor functional performance in upper body older women. ergometry. Levesque et al. 9 male 20g CrM or placebo 3 x 25.2km sprint CrM did not enhance repetitive sprints 2007 cyclists per day for 6 days trials with 5 x 200m when intense activities occur between sprints every 5km. bouts. Basta et al. 20 elite 20g of CrM or placebo Graded rowing on CrM did not increase rowers power on rowers per day for 5 days then ergometer ergometer. 10g daily for 30 days Ferguson et al. 26 resistance CrM 0.3g kg BM for Resistance training 4 CrM + resistance training did not improve trained first 7 days then days per week strength or lean body mass more than fe 0.03g kg BM for the resistance training only. next 9 weeks Glaister et al. 42 physically 5g CrM 4 x per day or 15 x 30m sprints CrM did not benefit multiple running sprint active placebo for 5 days repeated at 35 sec performances intervals

9 Watson et al. 12 active 21.6g per day of CrM Once 2% dehydrated, t applicable Short term CrM did not increase the or placebo for 7 days subjects completed incidence of symptoms or comprise an 80 min exercise hydration status in dehydrated men. heat tolerance test which involved 4 min rest, 3 min walk, 1 min high intensity run. Havenetidis et al male active subjects 25g of CrM for 4 days 3 x Wingate tests CrM Supplementation increased muscle ATP and creatine phosphate and enhanced performance in the Wingate test. References: Barros, M.P., Ganini, D., Loren\cco-Lima, L., Soares, C.O., Pereira, B., Bechara, E.J., Silveira, L.R., Curi, R., Souza-Junior, T.P., Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test. Journal of the International Society of Sports Nutrition 9, Beis, L.Y., Polyviou, T, Malkova, D, Pitsiladis, Y.P., The Effects of Craetien and Glycerol Hyperhydration on Running Economy in Well-Trained Endurance Runners. J Int Soc Sport Nutr. 8:24. Bemben MG, Lamont HS. Creatine supplementation and exercise performance: recent findings. Sports Med. 2005;35(2): Buford, T.W., Kreider, R.B, Stout, J.R, Greenwood, M, Campbell, B, Spano, M, Ziegenfuss, T, Lopez, H, Landis, J, Antonio, J., International Society of Sports Nutrition Position Stand: Creatine Supplementation and Exercise. J Int Soc Sport Nutr. 4:6 Burke LM and Deakin V. Clinical Sports Nutrition. 2nd ed. Australia: McGraw-Hill Book Company. (2003) Burke, D.G., Candow, D.G, Chilibeck, P.D, MacNeil, L.G, Roy, B.D, Tarnopolsky, M.A, Ziegenfuss, T., Effect of Creatine Supplementation and Resistance Exercise Training on Muscle Insulin-like Growth Factor in Young Adults. In J Sport Nutr Exerc Metab. 18: Cook, C.J., Crewther, B.T., Kilduff, L.P., Drawer, S., Gaviglio, C.M., Skill execution and sleep deprivation: effects of acute caffeine or creatine supplementation-a randomized placebo-controlled trial. Journal of the international society of sports nutrition 8, 1 8. Cooper, R., Naclerio, F., Allgrove, J., Jimenez, A., Creatine supplementation with specific view to exercise/sports performance: an update. Journal of the International Society of Sports Nutrition 9, 33.

10 Cribb, P.G., Williams, A.D, Hayes, A., A Creatine-Protein-Carbohydrate Supplement Enhances Responses to Resistance Training. Med Sci Sports Exerc. 39(11): De Oca, R.M.-M., Farfán-González, F., Socorro Camarillo-Romero, P., Efectos de la suplementación con creatina en practicantes de taekwondo. Nutrición Hospitalaria 28. Deminice, R., Rosa, F.T., Franco, G.S., Cunha, S.F.C., Freitas, E.C., Jordao, A.A., Shortterm creatine supplementation does not reduce increased homocysteine concentration induced by acute exercise in humans. European Journal of Nutrition. Gill ND, Hall RD, Blazevich AJ. Creatine serum is not as effective as creatine powder for improving cycle sprint performance in competitive male team-sport athletes. J Strength Cond Res. 2004;18(2): Harris RC, Almada AL, Harris DB, Dunnett M, Hespel P. The creatine content of Creatine Serum and the change in the plasma concentration with ingestion of a single dose. J Sports Sci Sep;22(9): McMorris, T., Harris, R.C., Swain, J., Corbett, J., Collard, K., Dyson, R.J., Dye, L., Hodgson, C., Draper, N.,. Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology 185, Moret, S., Prevarin, A., Tubaro, F., Levels of creatine, organic contaminants and heavy metals in creatine dietary supplements. Food Chemistry 126, Percário, S., de Tarso Domingues, S.P., Teixeira, L.F.M., Vieira, J.L.F., de Vasconcelos, F., Ciarrocchi, D.M., Almeida, E.D., Conte, M., Effects of creatine supplementation on oxidative stress profile of athletes. Journal of the International Society of Sports Nutrition 9, 56. Persky, A.M., Brazeau, G. a & Hochhaus, G., Pharmacokinetics of the dietary supplement creatine. Clinical pharmacokinetics, 42(6): Rahimi, R., Creatine supplementation decreases oxidative DNA damage and lipid peroxidation induced by a single bout of resistance exercise. The Journal of Strength & Conditioning Research 25, Schoch, R.D., Willoughby, D. & Greenwood, M.,. The regulation and expression of the creatine transporter: a brief review of creatine supplementation in humans and animals. Journal of the International Society of Sports Nutrition, 3(1): Sculthorpe N., Grace F, Jones P, Fletcher I., The effect of short-term creatine loading on active range of movement. Appl Physiol Nutr Metab 35: Tang, F.-C., Chan, C.-C., Kuo, P.-L., Contribution of creatine to protein homeostasis in athletes after endurance and sprint running. European Journal of Nutrition 53, Williams, P.G., Nutritional composition of red meat. Nutrition and Dietetics, 64 (4): Zuniga, J.M., Housh, T.J., Camic, C.L., Hendrix, C.R., Mielke, M., Johnson, G.O., Housh, D.J., Schmidt, R.J., The effects of creatine monohydrate loading on anaerobic performance

11 and one-repetition maximum strength. The Journal of Strength & Conditioning Research 26,